Subcellular distribution and activation of rat submandibular cAMP-dependent protein kinase following β-adrenergic receptor stimulation

1. Previous studies have shown that beta-adrenergic receptor activation has many effects on neuronal function in hippocampal area CA1. However, all of the physiological effects of beta-adrenergic receptor activation in this region reported to date have been attributed to postsynaptic mechanisms. A series of studies was performed to test the hypothesis that beta-adrenergic receptor activation also acts presynaptically to enhance excitatory synaptic transmission. 2. Application of the selective beta-adrenergic agonist isoproterenol to hippocampal slices induced an increase in the amplitude of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal cells. This response was potentiated in the presence of a cyclic nucleotide phosphodiesterase inhibitor. Isoproterenol also resulted in the appearance of a late inward synaptic current that likely represents polysynaptically evoked EPSCs. Both the increased amplitude of the monosynaptic EPSC and the appearance of polysynaptic EPSCs in response to isoproterenol were blocked by H89, an inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. 3. Isoproterenol induced an increase in the frequency of spontaneous miniature EPSCs but did not affect the amplitude of these currents. In addition, isoproterenol had no effect on currents elicited by direct application of the ionotropic glutamate receptor agonist, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 4. These results suggest that activation of presynaptic beta-adrenergic receptors enhances synaptic transmission in area CA1 via activation of cAMP-dependent protein kinase.

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Phosphorylation of the Third Intracellular Loop of the Mouse α 1b -Adrenergic Receptor by cAMP-dependent Protein Kinase

Brain Research Bulletin ◽

10.1016/s0361-9230(97)89758-4 ◽

1997 ◽

Vol 42 (6) ◽

pp. 427-430 ◽

Cited By ~ 2

Author(s):

Ana Alonso-Llamazares ◽

Emilio Casanova ◽

Daniel Zamanillo ◽

Sergio Ovalle ◽

Pedro Calvo ◽

...

Keyword(s):

Protein Kinase ◽

Adrenergic Receptor ◽

Intracellular Loop ◽

Dependent Protein Kinase ◽

The Third ◽

Camp Dependent Protein Kinase ◽

Third Intracellular Loop ◽

Dependent Protein

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Subcellular distribution in cerebral cortex of two proteins phosphorylated by a cAMP-dependent protein kinase.

The Journal of Cell Biology ◽

10.1083/jcb.83.2.308 ◽

1979 ◽

Vol 83 (2) ◽

pp. 308-319 ◽

Cited By ~ 140

Author(s):

T Ueda ◽

P Greengard ◽

K Berzins ◽

R S Cohen ◽

F Blomberg ◽

...

Keyword(s):

Cerebral Cortex ◽

Protein Kinase ◽

Synaptic Vesicle ◽

Subcellular Distribution ◽

Postsynaptic Density ◽

Mammalian Brain ◽

Dependent Protein Kinase ◽

Density Fraction ◽

Camp Dependent Protein Kinase ◽

Dependent Protein

The subcellular distribution of Proteins Ia and Ib, two proteins which serve as specific substrates for protein kinases present in mammalian brain, was studied in the dog cerebral cortex. Proteins Ia and Ib were found to be most highly enriched in synaptic vesicle fractions; they were also present in postsynaptic density and synaptic membrane fractions in significant amounts. Proteins Ia and Ib present in the synaptic vesicle fraction appear to be similar, if not identical, to those present in the postsynaptic density fraction as judged by several criteria: (a) the ability to serve as substrate for cAMP-dependent protein kinase, (b) electrophoretic mobility in the presence of sodium dodecyl sulfate, (c) extractability with NH4Cl or EGTA, and (d) fragmentation to electrophoretically similar peptides by a purified Staphylococcus aureus protease. In addition, the postsynaptic density fraction has been found to contain cAMP-dependent Protein Ia and Protein Ib kinase activity. The subcellular localization of Proteins Ia and Ib suggests a role for these proteins in the physiology of the synapse.

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